Previous investigation has demonstrated the presence of different types of anti-lymphocyte antibodies wth multiple antigenic specificities for both T and B lymphocytes in the sera of patients with systemic lupus erythematosus (SLE). Similar antibodies also are found in rheumatoid arthritis (RA) and chronic lymphocytic leukemia (CLL). Current evidence suggests that these antibodies may be of fundamental importance regarding basic immunologic alterations in these diseases. Initially the projected experiments are designed to characterize anti-lymphocyte autoantibodies in terms of immunoglobulin class, avidity and reactive lymphocyte subpopulations utilizing immunochemical techniques and cytotoxicity and indirect immunofluorescence assays. Characterized, isolated antibodies will be used as probes to define the exact nature of the reactive membrane determinants of both normal and patient lymphocytes. The biological effects of well-defined anti-lymphocyte antibodies on a variety of in vitro immune systems will be studied in order to define the basis for in vivo immunologic alterations. This will include the study of B and T cells from patients at various stages of their illness. The role anti-lymphocyte antibodies play in the natural history of SLE, RA and CLL will be defined. In addition, the nature and pathogenetic significance for tissue injury of immune complexes of shed lymphocyte antigen and specific antibody will be studied. Investigations are also planned to further elucidate the relationship between anti-lymphocyte antibodies and proposed basic etiologic factors in SLE, i.e., genetic and viral.